Our studies have been aimed at determining the molecular mechanism by which reticulum cell sarcoma (RCS) stimulate syngeneic lymphocytes from SJL/J mice. Our studies have shown antigens coded for by the I region of the MHC (i.e., antigens expressed on RCS tumor cells but not on host cells). We have been able to demonstrate the presence of these antigens by serological analysis using monoclonal antibodies directed against Ia7 specificity. In addition, we have shown that lymphocytes stimuated to RCS can bind both tumor cells and Ia7-bearing lymphocytes. In recent studies, we have been able to generate T-cell hybridomas responding to the RCS cells and Ia7-bearing cells but not to the host SJL/J lymphocytes. While the hybridoma response to Ia7 allogeneic cells were easily blocked by anti-Ia-7 monoclonal antibodies, the antitumor responses were weakly responsive and could also be blocked by anti-IAs antibodies. These results demonstrate that the recognition of Ia7 on tumor cells by T cells may be the result of epitopes cross-reactive or associated with IA antigens. We have also analyzed the response of the host to the tumor cells by characterizing several lymphokines (IL-2, IL-1, and CSF) derived from the stimulating cells. The contribution of the stimulator cells explains the nature of the high syngeneic response seen in this tumor system. Further studies also demonstrated the role of host IA-bearing cells in regulating tumor growth. This was done by the administration in vivo of monoclonal antibodies directed against Ia specificities resulting in strict interrelationship between host cells and tumor cells as well as the role of various antigenic determinants on tumor cells that are responsible for proliferation. The regulation of the host response to tumor has been shown to be under the influence of several factors, primarily serum lipoproteins that inhibit IL-2-dependent T-cell proliferative responses and the generation of T-suppressor cells which inhibit the syngeneic response. The present studies are aimed at characterizing the nature of these various cell-cell interactions, suppressive factors, and serum lipoproteins and lymphokines in tumor development. (IB)